Faculty Profiles - OUCHIDA Mamoru

TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers

Takayuki Sonoyama, Akiko Sakai, Yuichiro Mita, Yukiko Yasuda, Hirofumi Kawamoto, Takahito Yagi, Masao Yoshioka, Tetsushige Mimura, Kei Nakachi, Mamoru Ouchida, Kazuhide Yamamoto, Kenji Shimizu

MOLECULAR MEDICINE REPORTS 4 ( 3 ) 489 - 495 2011.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Tumor protein p53 (TP53) is the best-known tumor suppressor gene and plays a crucial role in carcinogenesis. The TP53 Arg 72 Pro polymorphism has been reported to be a risk factor for several types of cancer, but its association with pancreatic cancer has not been fully evaluated. Therefore, we investigated the effects of this polymorphism on pancreatic cancer in relation to smoking and drinking habits by examining the distribution of the SNP genotypes in 226 pancreatic cancer patients and 448 healthy controls. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro were found to be 37, 49 and 15% in the pancreatic cancer cases and 44, 46 and 10% in the controls, respectively. Compared to the controls with the Arg/Arg genotype, cases with Pro/Pro homozygosity exhibited a significantly increased risk [adjusted odds ratio (OR)=1.70; 95% confidence interval (CI) 1.01-2.88]. In stratified studies, the association was particularly strong in males (OR=2.62; 95% CI 1.32-5.23), particularly in those smoking in excess of 20 pack-years and drinking in excess of 23 g ethanol/day (OR=5.02; 95% CI 1.12-22.51). We found that the. TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.

DOI： 10.3892/mmr.2011.449

Therapy for hyperthermia-induced seizures in Scn1a mutant rats International journal

Keiichiro Hayashi, Satoshi Ueshima, Mamoru Ouchida, Tomoji Mashimo, Teiichi Nishiki, Toshiaki Sendo, Tadao Serikawa, Hideki Matsui, Iori Ohmori

EPILEPSIA 52 ( 5 ) 1010 - 1017 2011.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Purpose: Mutations in the SCN1A gene, which encodes the alpha 1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats.
Methods: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45 degrees C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test.
Key Findings: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance.
Significance: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.

DOI： 10.1111/j.1528-1167.2011.03046.x

Proteomic Analysis Reveals Aberrant Retinol Metabolism in Hepatitis C Virus Subgenomic Replicon-Harboring Cells

Kazuko Koike, Akinobu Takaki, Nobuyuki Kato, Mamoru Ouchida, Tetsuya Yasunaka, Yasuhiro Miyake, Kazuhide Yamamoto

GASTROENTEROLOGY 140 ( 5 ) S972 - S972 2011.5

Decoy strategy targeting the brain-derived neurotrophic factor exon I to attenuate tactile allodynia in the neuropathic pain model of rats International journal

Norihiko Obata, Satoshi Mizobuchi, Yoshitaro Itano, Yoshikazu Matsuoka, Ryuji Kaku, Naoto Tomotsuka, Kiyoshi Morita, Hirotaka Kanzaki, Mamoru Ouchida, Masataka Yokoyama

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 408 ( 1 ) 139 - 144 2011.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

The mechanism underlying neuropathic pain is still largely unclear. Recently, much attention has been focused on the role of brain-derived neurotrophic factor (BDNF) as a neuromodulator in the spinal cord. We previously reported that the expression of Bdnf exon I mRNA was remarkably up-regulated in the dorsal root ganglion (DRG) neurons with the rat L5 spinal nerve ligation (SNL) model. In the present study, we investigated whether neuropathic pain response would be reduced by the inhibition of the Bdnf exon I in the rat SNL model. We identified the promoter region of exon I and synthesized the decoy ODNs targeting the region. Reverse transcription-polymerase chain reaction analysis confirmed that the decoy ODN treatment reduced SNL-induced Bdnf exon I mRNA up-regulation in ipsilateral L4 and L5 DRGs. Furthermore, post-treatment with the decoy ODNs significantly attenuated SNL-induced tactile allodynia. This study suggested that decoy ODNs targeting the Bdnf exon I might provide a novel analgesic strategy for the treatment of neuropathic pain. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.03.137

Cumulative epigenetic abnormalities in host genes with viral and microbial infection during initiation and progression of malignant lymphoma/leukemia International journal

Takashi Oka, Hiaki Sato, Mamoru Ouchida, Atae Utsunomiya, Tadashi Yoshino

Cancers 3 ( 1 ) 568 - 581 2011.3

Language：English Publishing type：Research paper (scientific journal)

Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed. © 2011 by the authors
licensee MDPI, Basel, Switzerland.

DOI： 10.3390/cancers3010568

Scopus

Elevated oxidative stress is associated with ventricular fibrillation episodes in patients with Brugada-type electrocardiogram without SCN5A mutation

Masamichi Tanaka, Kazufumi Nakamura, Kengo Fukushima Kusano, Hiroshi Morita, Keiko Ohta-Ogo, Daiji Miura, Aya Miura, Koji Nakagawa, Takeshi Tada, Masato Murakami, Nobuhiro Nishii, Satoshi Nagase, Yoshiki Hata, Kunihisa Kohno, Mamoru Ouchida, Kenji Shimizu, Chikao Yutani, Tohru Ohe, Hiroshi Ito

Cardiovascular Pathology 20 ( 1 ) e37 - e42 2011.1

Language：English Publishing type：Research paper (scientific journal)

Background: Brugada syndrome is a disease known to cause ventricular fibrillation with a structurally normal heart and is linked to SCN5A gene mutation. However, the mechanism by which ventricular fibrillation develops in cases of Brugada-type electrocardiogram without SCN5A mutation has remained unclear. Recently, oxidative stress has been implicated in the pathophysiology of cardiac arrhythmia. We also investigated oxidative stress levels in the myocardia of patients with Brugada-type electrocardiogram. Methods: Endomyocardial biopsy samples were obtained from 68 patients with Brugada-type electrocardiogram (66 males and two females). We performed histological and immunohistochemical analyses for CD45, CD68, and 4-hydroxy-2-nonenal-modified protein, which is a major lipid peroxidation product. Results: SCN5A mutation was detected in 14 patients. Ventricular fibrillation was documented in three patients with SCN5A mutation and in 11 without SCN5A mutation. In patients with SCN5A mutation, 4-hydroxy-2-nonenal-modified protein-positive area was not significantly different between the documented ventricular fibrillation (VF) group (VF+ group) and the group without documented VF (VF- group). However, in patients without SCN5A, the area was significantly larger in the VF+ group than that in the VF- group (P&lt
.05). All other parameters (fibrosis area, CD45, and CD68) were not different between the VF+ and VF- group in both SCN5A+ and SCN5A- patients. Conclusion: Oxidative stress is elevated in the myocardium of patients with Brugada-type electrocardiogram who have VF episodes and do not have SCN5A gene mutations. Oxidative stress may be associated with the occurrence of VF in patients with Brugada-type electrocardiogram without SCN5A mutation. © 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.carpath.2010.02.002

Scopus

Cumulative kinetics of epigenetic abnormalities during initiation and progression of Adult T-cell Leukemia/Lymphoma (ATLL).

Oka T, Sato H, A Al-Kader L, Shinnou Y, Washio K, Takata K, Murakami I, Utsunomiya A, Ouchida M, Takahashi K, Yoshino T

Retrovirology 8 ( Suppl 1 ) 195 - 195 2011

Electrophysiological properties of variant voltage-gated calcium channels in patients with epilepsy

Iori Ohmori, Mamoru Ouchida, Haijiao Wang, Yuichiro Kitagawa, Hiroyuki Michiue, Teiichi Nishiki, Hideki Matsui

NEUROSCIENCE RESEARCH 71 E294 - E294 2011

Genetic seizure susceptibility underlying acute encephalopathies in childhood International journal

Katsuhiro Kobayashi, Mamoru Ouchida, Akihisa Okumura, Yoshihiro Maegaki, Itsuko Nishiyama, Hideki Matsui, Yoko Ohtsuka, Iori Ohmori

EPILEPSY RESEARCH 91 ( 2-3 ) 143 - 152 2010.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of the neuronal sodium channel alpha 1 subunit (SCN1A) gene which is the most representative gene for hyperthermia-induced seizure susceptibility.
Six patients (40%) had a positive family history of seizures or AE, especially febrile seizures, in first- or second-degree relatives. The SCN1A-R1575C mutation was detected in a patient with a history of acute encephalitis with refractory, repetitive partial seizures (AERRPS) and also in the patient's apparently healthy father.
In the present study, dense familial seizure predisposition was present in the patients with AE. Although the presence of seizure susceptibility alone is insufficient to cause AE, it can exacerbate seizures and the subsequent development of inflammatory reactions in the brain when environmental factors are included. Genetic seizure susceptibility may contribute to some types of AE in childhood. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.eplepsyres.2010.07.005

A Missense Mutation of the Gene Encoding Voltage-Dependent Sodium Channel (Na(v)1.1) Confers Susceptibility to Febrile Seizures in Rats International journal

Tomoji Mashimo, Iori Ohmori, Mamoru Ouchida, Yukihiro Ohno, Toshiko Tsurumi, Takafumi Miki, Minoru Wakamori, Shizuka Ishihara, Takashi Yoshida, Akiko Takizawa, Megumi Kato, Masumi Hirabayashi, Masashi Sasa, Yasuo Mori, Tadao Serikawa

JOURNAL OF NEUROSCIENCE 30 ( 16 ) 5744 - 5753 2010.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SOC NEUROSCIENCE

Although febrile seizures (FSs) are the most common convulsive syndrome in infants and childhood, the etiology of FSs has remained unclarified. Several missense mutations of the Na(v)1.1 channel (SCN1A), which alter channel properties, have been reported in a familial syndrome of GEFS+ (generalized epilepsy with febrile seizures plus). Here, we generated Scn1a-targeted rats carrying a missense mutation (N1417H) in the third pore region of the sodium channel by gene-driven ENU (N-ethyl-N-nitrosourea) mutagenesis. Despite their normal appearance under ordinary circumstances, Scn1a mutant rats exhibited remarkably high susceptibility to hyperthermia-induced seizures, which involve generalized clonic and/or tonic-clonic convulsions with paroxysmal epileptiform discharges. Whole-cell patch-clamp recordings from HEK cells expressing N1417H mutant channels and from hippocampal GABAergic interneurons of N1417H mutant rats revealed a significant shift of the inactivation curve in the hyperpolarizing direction. In addition, clamp recordings clearly showed the reduction in action potential amplitude in the hippocampal interneurons of these rats. These findings suggest that a missense mutation (N1417H) of the Na(v)1.1 channel confers susceptibility to FS and the impaired biophysical properties of inhibitory GABAergic neurons underlie one of the mechanisms of FS.

DOI： 10.1523/JNEUROSCI.3360-09.2010

Identification of novel direct targets of miR-19a in MCF-7 breast cancer cells

Hirotaka Kanzaki, Mamoru Ouchida, Sachio Ito, Seiji Tamaru, Hiroko Hanafusa, Yoshimi Jitsumori, Takashi Oka, Kenji Shimizu

CANCER RESEARCH 70 2010.4

Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers International journal

Yuichiro Mita, Yukiko Yasuda, Akiko Sakai, Hiromasa Yamamoto, Shinichi Toyooka, Mehmet Gunduz, Shunsuke Tanabe, Yoshio Naomoto, Mamoru Ouchida, Kenji Shimizu

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 136 ( 2 ) 249 - 259 2010.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

We investigated the association between incidence of various cancers and four single nucleotide polymorphisms (SNPs), two each in two protein tyrosine phosphatase (PTP) genes, PTPRJ and PTPN13, by a case-control study conducted in Japan.
The study samples comprised 819 cancer-free controls and 569 cancer cases including lung, head and neck, colorectal, and esophageal cancers.
Compared with the major homozygotes at the Arg326Gln SNP in PTPRJ, a likely homologue of the mouse SCC1 (susceptible to colon cancer), Arg/Gln or Gln/Gln genotypes exhibited an increased colorectal cancer risk with adjusted odds ratios (aOR) of 1.71 (P = 0.021) and 3.74 (P = 4.14 x 10(-4)), respectively. Increased risks were observed with one or more of the combination genotypes of Gln276Pro and Arg326Gln in PTPRJ for most cancer types (aOR range 10.13-55.08, Bonferroni-corrected P = 0.0454-7.20 x 10(-9)). In the PTPN13, major homozygotes of Ile1522Met showed an increased risk for lung squamous cell carcinomas (aOR 1.86), compared to the heterozygotes. Increased risks were observed with at least one of the combination genotypes of the two SNPs, Ile1522Met and Tyr2081Asp, for all but esophageal cancer examined (aOR 3.36-13.75), compared with double heterozygotes. Moreover, these high risks were seen also when all cancer cases were combined (aOR 1.81-6.84).
PTPRJ and PTPN13 SNPs were found to influence susceptibility to a wide spectrum of cancers. Because allelic frequencies of these SNPs are relatively common in many ethnic groups, these findings are worthy of further study.

DOI： 10.1007/s00432-009-0656-7

Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2'-deoxycytidine against synovial sarcoma cell lines International journal

Kunihiko Numoto, Aki Yoshida, Shinsuke Sugihara, Toshiyuki Kunisada, Yuki Morimoto, Yasushi Yoneda, Yasuko Fujita, Keiichiro Nishida, Mamoru Ouchida, Toshifumi Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 136 ( 1 ) 17 - 25 2010.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of de-methylation on synovial sarcoma were examined.
The methylation status in 74 soft tissue sarcomas (STSs) including 21 synovial sarcomas was determined by methylation specific PCR. The effect of the de-methylating agent 5-aza-2'-deoxycytidine (5-Aza-dC) on synovial sarcoma was examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II).
RASSF1A methylation was observed in 10 (47.6%) of 21 synovial sarcomas and in 10 (18.9%) of 53 the other STSs (P = 0.0295). De-methylation of the cells by treatment with 5-Aza-dC induced re-expression of RASSF1A and growth suppression of the cells. The calculated IC50 of 5-Aza-dC against the SYO-1 and the HS-SY-II cells were 0.9 and 1.3 mu M (96 h), respectively. With twice weekly administration of 1 or 10 mg/kg 5-Aza-dC, the growth of the mouse xenograft tumors of SYO-1 was significantly suppressed in comparison to the controls (P < 0.01).
This is the first report showing the anti-tumor effect of 5-Aza-dC on synovial sarcoma. 5-Aza-dC is suggested to have a good therapeutic potential against synovial sarcoma.

DOI： 10.1007/s00432-009-0632-2

Multi-Step Aberrant CpG Island Hyper-Methylation Is Associated with the Progression of Adult T-Cell Leukemia/Lymphoma International journal

Hiaki Sato, Takashi Oka, Yoko Shinnou, Takami Kondo, Kana Washio, Masayuki Takano, Katsuyoshi Takata, Toshiaki Morito, Xingang Huang, Maiko Tamura, Yuta Kitamura, Nobuya Ohara, Mamoru Ouchida, Koichi Ohshima, Kenji Shimizu, Mitsune Tanimoto, Kiyoshi Takahashi, Masao Matsuoka, Atae Utsunomiya, Tadashi Yoshino

AMERICAN JOURNAL OF PATHOLOGY 176 ( 1 ) 402 - 415 2010.1

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC INVESTIGATIVE PATHOLOGY, INC

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers. (Am J Pathol 2010, 176:402-415; DOI: 10.2353/ajpath.2010.090236)

DOI： 10.2353/ajpath.2010.090236

Multi-step accumulation of aberrant CpG island hypermethylation in specific genes promotes development and progression of lymphomas/leukemias

Takashi Oka, Hiaki Sato, Takami Kondo, Yoko Shinnou, Kana Washio, Ichiro Murakami, A. B. D. Al-Kader Lamia, Xu Sun, Katsuyoshi Takata, Mamoru Ouchida, Koichi Ohshima, Mitsune Tanimoto, Atae Utsunomiya, Kiyoshi Takahashi, Tadashi Yoshino

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 26 ( Sup1 ) S44 - S44 2010

A CACNB4 mutation shows altered Cav2.1 function in a patient with Dravet syndrome

大守伊織, 大内田守, 御牧信義, 西木禎一, 富澤一仁, 松井秀樹

岡山医学会雑誌 121 ( 3 ) 149 - 156 2010

Helicobacter pylori infection induce accumulation of aberrant CpG hypermethylation to promote development and progression of gastric MALT lymphoma

Takashi Oka, Takami Kondo, Hiaki Sat, Yoko Shinnou, Kana Washio, Toshiaki Morit, Katsuyoshi Takat, Nobuya Ohara, Mamoru Ouchida, Kenji Shimizu, Tadashi Yoshin

Proceedings of The 3rd International Symposium for Future Technology Creating Better Human Health and Society Comprehensive Approach to Cancer and Infectious Diseases 1 ( 1 ) 105 - 105 2010

REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells International journal

Jie Chen, Masami Watanabe, Peng Huang, Masakiyo Sakaguchi, Kazuhiko Ochiai, Yasutomo Nasu, Mamoru Ouchida, Nam-Ho Huh, Kenji Shimizu, Yuji Kashiwakura, Haruki Kaku, Hiromi Kumon

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 24 ( 6 ) 789 - 794 2009.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3. a member of the Dkk gene family, is a tumor suppressor in a broad range of cancers. REIC/Dkk-3 transfected stable clones of mouse prostate cancer RM9 cells (RM9-REIC) and the empty vector-transfected control clone cells (RM9-EV) were established. Clones were used to evaluate the anti-cancer effects and a proteomics analysis of REIC/Dkk-3 continuous expression was performed. The RM9-REIC cells show a feeble appearance and the cell membrane shows irregular buds known as blebs. In vitro cell proliferation was significantly suppressed in RM9-REIC clones in comparison to the control. The apoptosis assay was done under standard culture conditions and RM9-REIC showed a higher incidence of apoptosis. The RM9-EV and RM9-REIC cells were orthotopically implanted into a C57BL/6 mouse prostate. After 2 weeks, the tumor growth was significantly inhibited in RM9-REIC cells in comparison to the control. Two-dimensional gel electrophoresis was used to examine the modification of protein expression by the gene transfection. The analysis with mass spectrometry disclosed that expression of peroxiredoxin-l, GST-P1. transgelin-2, MRP-L12, ARD, GRP78 and Sorcin were increased and eEF1A-1 and cyclophilin-40 protein were decreased in RM9-REIC cells. Therefore, REIC/Dkk-3 stable transfectants show a reduction of malignancy in mouse prostate cancer RM9 cells in vitro and in vivo. The result of the proteomics analysis might provide important clues to clarify the anti-cancer molecular mechanism of REIC/Dkk-3 gene transfer.

DOI： 10.3892/ijmm_00000293

Dravet症候群患者に認められたカルシウムチャネル機能異常を引き起こすCACNB4遺伝子変異

大守伊織, 大内田守, 御牧信義, 西木禎一, 富澤一仁, 松井秀樹

岡山医学会雑誌 121 ( 3 ) 149 - 156 2009.12

Language：Japanese Publisher：岡山医学会

Dravet症候群患者に認められたカルシウムチャネル機能異常を引き起こすCACNB4遺伝子変異について検討した。SCN1A遺伝子解析で変異を認めたDravet症候群患者38例を対象とした。健常者200例を対照とした。Dravet症候群患者で、SCN1B遺伝子とGABRG2遺伝子に変異を持つ症例はなかったが、CACNB4遺伝子変異を持つ症例を1例見出した。全細胞記録では、R568X変異からは背景電流異常のナトリウム電流は認めなかった。変異チャネルが野生型に比し有意にBa2+電流が増大した。ピーク電圧、細胞キャパシタンス、電流密度も変異型が野生型よりも有意に高値であった。